P64 A CASE OF COVID-19 PNEUMONIA AFTER CAR T-CELL THERAPY IN A PATIENT AFFECTED BY RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: C. Ielo, F. Fazio, S. Rocchi, I. Rizzello, E. Zamagni, MT Petrucci
Journal: HemaSphere (2023)

BCMA-targeting chimeric antigen receptor (CAR) T cells proved extremely effective in the treatment of relapsed/refractory (RR) multiple myeloma (MM). Nevertheless, their impact on immune system along with immune impairment induced by previous treatments and MM itself could determine vulnerability to infectious events. COVID-19 could evolve into a life-threating infection in MM patients especially in those with RR disease. Moreover, immune response to SARS-CoV-2 vaccines in this patient population could be suboptimal preventing adequate protection against COVID-19 complications. We report a case of a 51-year-old woman with anaemia and rib fractures diagnosed with IgG-k MM in 2012. Serum monoclonal component was 6.3 g/dl and Bence Jones proteinuria was 2.3 g/24h. Cytogenetic analysis showed amplification of 1q21 and, according to the International Staging System (ISS) and Revised-ISS, the disease was classified as stage I and I, respectively. After taking part in the EMN02 trial, the patient received 4 induction cycles with bortezomib, cyclophosphamide and dexamethasone, followed by tandem autologous stem cell transplantation and 2 consolidation cycles with bortezomib, lenalidomide and dexamethasone. Complete remission was achieved at the end of consolidation and maintained with lenalidomide until 2020 when she experienced clinical relapse. Subsequent treatment consisted of 8 cycles of induction therapy with carfilzomib, pomalidomide and dexamethasone followed by maintenance with pomalidomide within the EMN11 trial and led to partial remission. After a few months, the patient experienced biochemical relapse and third line therapy with daratumumab, lenalidomide and dexamethasone was started. Due to refractoriness to the last therapy, the patient was enrolled in the CARTITUDE-4 trial and randomized to receive CAR T- cell therapy in December 2021. On third day post-infusion, grade 2 cytokine release syndrome developed and resolved with tocilizumab and steroids. Minimal residual disease (MRD) negativity has been achieved 6 months after infusion. In July 2022 the patient contracted SARS-CoV-2 infection. She had been vaccinated against COVID-19 and received a third boost in March 2022. Despite antiviral therapy with molnupiravir, cough worsened, and bilateral interstitial pneumonia was detected by CT scan (Fig.1) on admission to hospital. Blood tests showed lymphopenia (800 cells/µl), severe hypogammaglobulinemia (200 mg/dl) and high levels of inflammatory markers (CRP 38000 µgr/l and IL-6 38 pg/ml). Remdesivir and tixagevimab-cilgavimab did not improve the clinical condition which was exacerbated by pulmonary embolism and required high-flow oxygen therapy. Viral genotyping revealed non BA.2 omicron variant, viremia resulted positive and antinucleocapsid antibodies were not identified. Analysis of lymphocyte subpopulation displayed B-cell aplasia (10 cells/µl), CD4+ T cells (200 cells/µl) and NK cells (37 cells/µl) deficiency. Hyper immune plasma was administered obtaining resolution of opacities and improvement of respiratory failure. Soon after pulmonary aspergillosis superimposed and resolved with isavuconazole. Viral clearance has been obtained 5 months after initial infection and the patient is still in complete remission with MRD negativity one year after CAR-T infusion. Long-term infectious complications in MM CAR-T recipients should be taken into consideration as they could counteract the efficacy of this treatment.